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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study evaluated the ability of alpha1-adrenergic blockade to interfere with the development of diet-induced hyperlipidemia and deterioration of insulin action. Diets having extremely divergent effects on glucose and lipid metabolism were contrasted. Rats were fed for 4 weeks either a nonpurified diet (chow) or a hyperlipidemic (HL) purified diet containing 40% energy as sucrose, 40% as fat, and 20% as casein. Half of each dietary cohort was given the alpha1-adrenergic antagonist prazosin (3 mg/kg/day in the food). Blood was collected in the fasted state (10 h after food removal) and 2 h after the intake of a meal. In the fasted state, plasma triacylglycerols (TGs) were higher in rats fed the HL diet than in those given chow and were not affected by long-term treatment with prazosin. Postprandially, plasma TG increased twofold in the chow-fed group, with or without long-term prazosin. In contrast, prazosin reduced by more than half the eightfold increase in TG that followed intake of the high-fat meal (Diet x Blocker interaction; p < 0.002) in the HL cohort. The HL-fed animals also displayed fasting hypercholesterolemia (+30%; p < 0.0001), which was prevented by long-term treatment with prazosin. Likewise, the 50% increase in plasma cholesterol that followed meal ingestion only in the HL cohort was blunted by the alpha1-blocker (Diet x Blocker interaction; p < 0.001). Long-term prazosin also abolished fasting hyperinsulinemia in the HL cohort, whereas it did not alter fasting insulin in chow-fed animals (Diet x Blocker interaction; p < 0.005). Measurement of postprandial lipoprotein lipase activity in several tissues did not suggest the involvement of changes in the absolute availability of the enzyme as a determinant of the hypotriacylglycerolemic action of the alpha1-blocker. Thus long-term alpha1-adrenergic blockade, with minimal effects in rats fed a hypolipidemic diet, strongly attenuates several of the fasting and postprandial alterations in plasma variables of lipid and glucose metabolism induced by an extremely lipogenic diet.
J Cardiovasc Pharmacol 1998 Dec
PMID:Long-term alpha1-adrenergic blockade attenuates diet-induced dyslipidemia and hyperinsulinemia in the rat. 986 96

Between February 1994 and January 1997, 102 of the 146 patients treated by coronary artery bypass grafting (CABG) had undergone magnetic resonance angiography (MRA) of the brain and neck before the operation, and arterial stenosis or occlusion had been detected in 38 (36.9%) of them. Two of these patients had complicating severe calcification of the ascending aorta, and CABG was performed without cardiopulmonary bypass (CPB). Seven patients without stenotic lesions on MRA were also treated by CABG without CPB for other complications. In addition to the 102 patients one patient had been found to have occlusion of the left common carotid artery and poor enhancement of the distal portion, and as a result we switched from CABG to percutaneous transluminal angioplasty (PTCA). We enrolled 93 patients in this study excluding these 10 patients. The patients were distributed into the three groups according to the MRA findings. Group C = no stenotic lesions (58 patients). Group S = stenosis of < 70% (26 patients), Group SS = stenosis of > or = 70% (9 patients). Enhancement distal to the stenotic or occlusive lesions was good in all patients in group S and SS. We then examined them for the incidence of postoperative neurological complications. There were no significant differences among the three groups in regard to age, male/female ratio, or incidence of hypertension and hyperlipidemia. In Group S, the incidence of diabetes was significantly higher than in the other Groups. The incidence of prior stroke was significantly higher and the number of coronary arteries affected was significantly larger in group SS than the other groups. There were no significant differences among the three groups with regard to intraoperative variables. The lowest mean arterial pressure on CPB was 44.3 +/- 7.4 mmHg, 48.0 +/- 8.8 mmHg, 46.3 +/- 7.8 mmHg in Group C, S, and SS, respectively, In all groups the lowest mean arterial pressure on CPB was below 50 mmHg. There were no significant differences among the three groups with regard to time to awaken and time to extubation. Two patients experienced transient conciousness disturbance after CABG, one in Group C, the other in Group SS, but no new lesions were detected by brain CT. Only one patient, in Group C. suffered a stroke and had a new lesion on brain CT a month after the operation. No strokes occurred in the perioperative period. In nine patients with good enhancement distal to the severe stenotic or occlusive lesion on MRA of the brain and neck the lowest mean arterial pressure on CPB was below 50 mmHg, but there was no postoperative neurological complications due to the low perfusion pressure on CPB. The results of this study suggested that CABG with CPB can be performed safely in patients with good enhancement distal to the stenotic or occlusive lesions on MRA of the brain and neck.
Jpn J Thorac Cardiovasc Surg 1998 Dec
PMID:[Preoperative magnetic resonance angiography findings and postoperative neurological complications in 93 cases of CABG with cardiopulmonary bypass]. 1003 31

BACKGROUND: Combination lipid-lowering therapy may be desirable in patients with elevated low-density lipoprotein cholesterol, high triglycerides, and low high-density lipoprotein cholesterol. This study was conducted to determine the lipid-lowering efficacy of the combination of low-dose simvastatin and niacin in patients with combined hyperlipidemia and low high-density lipoprotein cholesterol. METHODS AND RESULTS: In this multicenter, prospective, randomized trial, 180 patients with hypercholesterolemia and hypertriglyceridemia and/or low high-density lipoprotein cholesterol were randomized to combination simvastatin (10 mg/day) and niacin (0.75 g/day) or to either drug alone for 9 weeks. The dose of niacin was doubled (from 0.75 g/day to 1.5 g/day) in both the combination and niacin arms for the remaining 8 weeks. The combination of simvastatin, 10 mg/day, and niacin, 1.5 g/day, reduced total, low-density lipoprotein, and very low-density lipoprotein cholesterol and triglycerides by 24%, 29%, 45%, and 31%, respectively, while increasing high-density lipoprotein cholesterol by 31%. The addition of niacin to simvastatin did not enhance the low-density lipoprotein cholesterol by 31%. The addition of niacin to simvastatin did not enhance the low-density lipoprotein cholesterol-lowering effect of simvastatin; however, the combination was more effective than either monotherapy at raising high-density lipoprotein cholesterol and lowering very low-density lipoprotein cholesterol (P <.05). More patients discontinued treatment because of an adverse event in the niacin (P <.03) and combination groups (P =.06) than the simvastatin group. CONCLUSIONS: Treatment of patients with combined hyperlipidemia and/or low high-density lipoprotein with combination low-dose simvastatin and niacin resulted in large reductions in total, low-density lipoprotein, and very low-density lipoprotein cholesterol and increases in HDL cholesterol. Although the combination was well tolerated in the current trial, its safety needs to be evaluated in larger trials of longer duration.
J Cardiovasc Pharmacol Ther 1996 Apr
PMID:Efficacy and Tolerability of Low-dose Simvastatin and Niacin, Alone and in Combination, in Patients With Combined Hyperlipidemia: A Prospective Trial. 1068 7

BACKGROUND: Atorvastatin, a new HMG-CoA reductase inhibitor in clinical development has demonstrated an acceptable safety profile and marked cholesterol and triglyceride reduction at doses ranging from 10-80 mg/day. Since bile acid sequestering resins are often used in combination with HMGRIs to enhance cholesterol reduction, this trial was conducted to explore the use of atorvastatin alone and combined with colestipol in patients with primary hyperlipidemia. METHODS AND RESULTS: One hundred six patients with low-density lipoprotein (LDL) cholesterol >4.1 mM/L (160 mg/dL) and plasma triglycerides <3.9 mM/L (350 mg/dL) were randomized to treatment consisting of 20 g/day colestipol, 10 mg/day atorvastatin, or 10 mg/day atorvastatin plus 20 g/day colestipol for 12 weeks. Percent change from baseline in lipid variables were measured. The atorvastatin group showed a significant reduction in LDL cholesterol of 35% after 12 weeks. Combination therapy provided an additional 10% reduction in LDL cholesterol over that observed for atorvastatin alone. Twenty-one percent of all patients in the atorvastatin monotherapy group experienced associated adverse events compared with 60% in the combination therapy group. Ninety percent of atorvastatin monotherapy patients were compliant at every visit compared with 75% receiving combination therapy. CONCLUSIONS: Although the combination of atorvastatin plus colestipol was more effective in lowering LDL cholesterol than atorvastatin alone, atorvastatin 10 mg/day monotherapy provided a better safety profile and improved patient compliance, which may result in improved long-term cholesterol control.
J Cardiovasc Pharmacol Ther 1996 Apr
PMID:Atorvastatin, a New HMG-CoA Reductase Inhibitor as Monotherapy and Combined With Colestipol. 1068 8

BACKGROUND: The present study was designed to determine the efficacy and safety of Niaspan (Kos Pharmaceuticals, Inc, Hollywood, FL), a new controlled-release formulation of niacin, in the treatment of primary hyperlipidemia, the occurrence and severity of flushing events, and potential adverse effects, particularly hepatotoxicity. METHODS AND RESULTS: The study was conducted as a multicenter, randomized, double-blind, placebo-controlled, parallel comparison of Niaspan in doses of 1000 mg/day and 2000 mg/day, administered once a day at bedtime. One hundred twenty-two patients with low-density lipoprotein cholesterol levels >4.14 mM/L (160 mg/dL) with dietary intervention and high-density lipoprotein cholesterol </=1.81 mM/L (70 mg/dL) were randomized to one of three treatment groups: placebo, and 1000 mg/day or 2000 mg/day of Niaspan. Safety and efficacy measures included 12-hour serum fasting lipid and lipoprotein concentrations, serum analyte levels for major organ function, flushing diaries, and adverse event records. The placebo group demonstrated no significant changes in serum lipoprotein concentrations over the treatment period of 12 weeks, except for a slight 4% increase in high-density lipoprotein cholesterol. Niaspan significantly lowered low-density lipoprotein cholesterol levels by 6% and 14% for the 1000 mg/day and 2000 mg/day doses, respectively. High-density lipoprotein cholesterol levels rose significantly, with a 17% increase occurring at the 1000 mg/day dose and a 23% increase occurring at the 2000 mg/day doses, respectively. High-density lipoprotein cholesterol levels rose significantly, with a 17% increase occurring at the 1000 mg/day dose and a 23% increase occurring at the 2000 mg/day dose. Niaspan (2000 mg/day) produced significant decreases of 27% and 29%, respectively, for serum lipoprotein(a) and triglyceride concentration. Although the incidence of flushing was significant, these episodes were generally well tolerated. CONCLUSION: Niaspan administered in doses of 1000 mg/day and 2000 mg/day at bedtime were well tolerated with few side effects and produced favorable effects on the major circulating lipoproteins of patients with primary dyslipidemias as specified by the enrollment criteria.
J Cardiovasc Pharmacol Ther 1996 Jul
PMID:Treatment Effect of Niaspan, a Controlled-release Niacin, in Patients With Hypercholesterolemia: A Placebo-controlled Trial. 1068 17

BACKGROUND: Pravastatin inhibits 3-hydroxy-3-methylglutaryl-coenzyme A reductase. It prevents mevalonate synthesis, reducing endogenous cholesterol production, and reduces cholesterol content in the liver, thus resulting in a down-regulation of low-density lipoprotein receptor production. Gemfibrozil reduces very low-density lipoprotein production and low-density lipoprotein-cholesterol level and increases very low-density lipoprotein catabolism. Therefore, it was suggested that combination therapy with both drugs could effect greater reduction of cholesterol levels as compared to pravastatin alone. The present study was carried out to evaluate the efficacy and safety of pravastatin as a monotherapy or in combination with gemfibrozil in the treatment of patients with familial type IIb hyperlipoproteinemia or familial combined hyperlipidemia. METHODS AND RESULTS: Forty-one patients were included in the study. All patients initially followed 6 weeks of hypolipidemic diet; subsequently they were randomized and received either 20 mg once daily of pravastatin alone (n = 13) or 20 mg of pravastatin together with 600 mg of gemfibrozil twice daily (n = 14). As a control, 14 patients were treated with diet only. The treatment lasted 24 months and clinical evaluation and laboratory tests were done at given time points. Both groups of treated patients showed an early reduction (3 months) of total (about 30% P <.01 vs controls), low-density lipoprotein (about 35%, P <.01 vs controls) and very low-density lipoprotein cholesterol levels (about 18%, P = NS). In contrast, high-density lipoprotein cholesterol levels increased significantly in patients treated with pravastatin and gemfibrozil (about 20%, P <.05 vs controls). Pravastatin treatment alone reduced the level of serum triglycerides as efficiently as in combination with gemfibrozil. Data showed a sustained normalization of lipid profile until 24 months. However, this effect was achieved in patients that had rather low levels of triglycerides. During the treatment we did not observe any difference in the incidence of possible drug-related side effects. Severe myopathy or rhabdomyolysis was not observed at the doses of the drugs used in our study. CONCLUSIONS: Therapy with pravastatin and in combination with gemfibrozil resulted in significant and sustained normalization of lipid profile in high-risk patients with familial type IIb hyperlipoproteinemia or familial combined hyperlipidemia.
J Cardiovasc Pharmacol Ther 1997 Jan
PMID:Long-term Treatment With Pravastatin Alone and in Combination With Gemfibrozil in Familial Type IIB Hyperlipoproteinemia or Combined Hyperlipidemia. 1068 38

Hyperlipidemia is an important cardiovascular risk factor. Lipid-lowering therapy has been shown to decrease morbidity and mortality in these patients. Combination therapy with a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor and a fibric-acid derivative has been reported to be more efficacious to reduce low-density lipoprotein (LDL) cholesterol and triglycerides but may be associated with an increased risk of myositis. The aim of this study was to investigate the efficacy and tolerability of fluvastatin, an HMG-CoA reductase inhibitor, alone and in combination with bezafibrate, a fibric-acid derivative. In a randomized controlled trial with 454 hypercholesterolemic patients (mean cholesterol, 8.6 +/- 1.6 mM), fluvastatin (20 mg/day) significantly lowered total plasma cholesterol levels (-12.5%; p < 0.0001 vs. placebo), LDL cholesterol (-14%; p < 0.0001), and triglycerides (-4%; p = 0.05). A small increase in high-density lipoprotein (HDL) cholesterol levels (3%, NS) also was observed. Combination therapy with fluvastatin and bezafibrate (400 mg/day) in 71 patients with persistent hypertriglyceridemia during treatment with the statin resulted in a more pronounced reduction in triglyceride (-47%; p < 0.0001) and total cholesterol levels (-15%; p < 0.0001) than did fluvastatin alone. Furthermore, the additional bezafibrate significantly increased HDL cholesterol (+5%; p < 0.001). No significant increases in creatine phosphokinase levels or in frequency of myalgia were observed. In summary, fluvastatin decreases both cholesterol and triglyceride levels. In patients with persistent hypertriglyceridemia, combination therapy with fluvastatin and bezafibrate may be safely used to lower triglyceride and cholesterol levels more efficiently.
J Cardiovasc Pharmacol 2000 Mar
PMID:Efficacy and tolerability of fluvastatin and bezafibrate in patients with hyperlipidemia and persistently high triglyceride levels. 1071 Jan 19

Pharmaceutical therapy of hyperlipidemia is clearly beneficial. In the patient without established heart disease however, conventional risk assessment is imprecise and determining which patients are at highest versus lowest risk is a common clinical conundrum. It is well established that the most powerful determinant to risk is the overall extent/severity of coronary disease. Electron beam tomography (EBT) and quantification of coronary artery calcium has been shown to provide a valid non-invasive surrogate to atherosclerotic plaque burden. Screening patients who are considered to be at traditional intermediate to high risk by first using EBT can refine the broad-based population risk to a more individual basis. Data that is based upon a model developed for application of EBT are presented, which discuss its potential as a cost effective application to guide statin therapy in intermediate and high-risk sub-groups.
J Cardiovasc Risk 2000 Apr
PMID:Cost effectiveness of coronary calcification scanning using electron beam tomography in intermediate and high risk asymptomatic individuals. 1087 14

Modifications by atherosclerosis of endothelium-dependent and -independent relaxations were evaluated in carotid arteries isolated from Watanabe heritable hyperlipidemic (WHHL; age 20-29 months) and age-matched Japanese white (JW) rabbits. Marked, patchy atherosclerotic lesions were observed in all WHHL rabbit arteries. Endothelium-dependent relaxations induced by acetylcholine, partly depressed by N(G)-nitro-L-arginine (L-NA), were significantly inhibited in the WHHL rabbit arteries with atherosclerosis, compared with those in the arteries without atherosclerotic lesions from JW and WHHL rabbits. No difference was observed in the relaxation caused by superoxide dismutase in these arteries. Conversely, endothelium-dependent relaxations by substance P were greater in the arteries with and without atherosclerosis from WHHL rabbits than in the arteries from JW rabbits. Endothelium-independent relaxations elicited by sodium nitroprusside and 2,2-(hydroxynitrosohydrazino)bis-ethanamine (NOC18) did not differ in the arteries from JW and WHHL rabbits. The responses to acetylcholine and substance P of JW rabbit arteries with the endothelium were not attenuated by treatment with pertussis toxin. L-NA-resistant, endothelium-dependent relaxations by substance P were almost abolished by charybdotoxin, and atherosclerosis did not alter the response. It is concluded that endothelial functions, evaluated by substance P, in rabbit carotid arteries are not impaired by atherosclerosis and by long exposure to hyperlipidemia in vivo. Dysfunction of muscarinic receptors may be involved in the depressed response to acetylcholine. As far as the arteries used in the present study are concerned, responses mediated possibly by endothelium-derived hyperpolarizing factor (EDHF) are unlikely to be modulated by atherosclerosis.
J Cardiovasc Pharmacol 2000 Nov
PMID:Comparison of endothelium-dependent relaxation in carotid arteries from Japanese white and Watanabe heritable hyperlipidemic rabbits. 1106 23

Several clinical studies have shown that the magnitude and duration of postprandial lipemia is positively related to the pathogenesis and progression of coronary heart disease. Postprandial lipid metabolism refers to the series of metabolic events that occur following the ingestion of a meal containing fat. Dietary fat is principally composed of triacylglycerol, postprandial lipaemia therefore being characterized by an increase in plasma triacylglycerol concentration. This review will describe the nature of the postprandial response and show the direct and indirect pro-atherogenic effects of triacylglycerol-rich lipoprotein metabolism. An elevated postprandial lipemic response precipitates a number of adverse metabolic events, including the production of atherogenic chylomicron remnants, the formation of the highly atherogenic small, dense low-density lipoprotein particles, and a reduction in the concentration of the cardioprotective high-density lipoprotein fraction. Postprandial lipemia also interacts with the process of thrombosis, in that an elevated postprandial triacylglycerol-rich lipoprotein concentration has the ability to activate the coagulation factor VII and plasminogen activator inhibitor. In the light of the potential impact of an elevated postprandial lipemia on atherothrombosis, the genetic determinants of the magnitude of the postprandial response will be identified. Finally, the nutritional factors that modulate the postprandial response will also be discussed.
J Cardiovasc Risk 2000 Oct
PMID:The impact of postprandial lipemia in accelerating atherothrombosis. 1114 61


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